A novel residual block: replace Conv1× 1 with Conv3×3 and stack more convolutions.

The residual structure has an important influence on the design of the neural network model. The neural network model based on residual structure has excellent performance in computer vision tasks. However, the performance of classical residual networks is restricted by the size of receptive fields, channel information, spatial information and other factors. In this article, a novel residual structure is proposed. We modify the identity mapping and down-sampling block to get greater effective receptive field, and its excellent performance in channel information fusion and spatial feature extraction is verified by ablation studies. In order to further verify its feature extraction capability, a non-deep convolutional neural network (CNN) was designed and tested on Cifar10 and Cifar100 benchmark platforms using a naive training method. Our network model achieves better performance than other mainstream networks under the same training parameters, the accuracy we achieved is 3.08 percentage point higher than ResNet50 and 1.38 percentage points higher than ResNeXt50. Compared with SeResNet152, it is 0.29 percentage point higher in the case of 50 epochs less training.

A single dose of Astragalus saponins adjuvanted inactivated vaccine for pseudorabies virus protected mice against lethal challenge.

Pseudorabies (PR) is an important infectious disease of swine that causes enormous economic losses to the swine industry in China. Immunization with vaccines is a routine practice to control this disease. PRV inactivated vaccines usually require a booster vaccination to provide complete immune protection. Therefore, Astragalus saponins (AST) have been added as an immunopotentiator to improve the immune efficacy and reduce the immunization times for the PRV inactivated vaccine. The results in mice have shown that a single dose of AST-adjuvanted PRV inactivated vaccine promoted higher production of gB-specific IgG, IgG1, and IgG2a and neutralizing antibody, secretion of Th1-type (IFN-γ) and Th2-type (IL-4) cytokines, and lymphocyte proliferation than mice immunized without AST. Compared to mice immunized without AST, a single dose of the AST-adjuvanted PRV inactivated vaccine improved the survival percentage of mice and reduced the PRV viral loads in the lungs and brains after lethal challenge. In summary, AST was an effective immunopotentiator to improve the immune efficacy of a single dose PRV inactivated vaccine.

Protective efficacy of intranasal inactivated pseudorabies vaccine is improved by combination adjuvant in mice.

Pseudorabies virus (PRV) not only causes great economic loss to the pig industry but also seriously threatens the biosafety of other mammals, including humans. Since 2011, PRV mutant strains have emerged widely in China, and the classical Bartha-K61 vaccine cannot confer complete protection for pigs. PRV mainly infects pigs via the respiratory tract. Intranasal immunization with PRV has received more attention because intranasal vaccination elicits systemic and mucosal immune responses. To induce systemic and mucosal immune responses against PRV, we developed a combination adjuvant as a delivery system for intranasal vaccine, which was formulated with MONTANIDE™ Gel 01 and CVCVA5. In comparison to naked antigen of inactivated PRV, single Gel 01 adjuvanted inactivated antigen and single CVCVA5 adjuvanted inactivated antigen, intranasal inactivated PRV vaccine formulated with the combination adjuvant induced greater mucosal IgA immunity and serum antibody responses (IgG, IgG1, and IgG2a). Furthermore, the production of the Th1-type cytokine IFN-γ and the Th2-type cytokine IL-4 indicated that the cellular and humoral responses to the intranasal vaccine were improved by the combination adjuvant. In addition, the intranasal vaccine formulated with the combination adjuvant induced long-term T lymphocyte memory with increased central (CD62L+CD44+) and effector (CD62L-CD44+) memory subsets of both CD4 and CD8 T cells in nasal-associated lymphoid tissue. Intranasal challenge with virulent PRV in mice showed that the protective efficacy of the intranasal PRV vaccine was improved by the combination adjuvant compared with the other single-adjuvanted vaccines. In summary, these data demonstrated that Gel 01 combined with the CVCVA5 adjuvant induced a synergistic effect to improve mucosal immunity and protective efficacy of the intranasally inactivated PRV vaccine in mice. It represents a promising vaccination approach against PRV infection.

Colossal Room-Temperature Terahertz Topological Response in Type-II Weyl Semimetal NbIrTe4.

The electromagnetic spectrum between microwave and infrared light is termed the "terahertz (THz) gap," of which there is an urgent lack of feasible and efficient room-temperature (RT) THz detectors. Type-II Weyl semimetals (WSMs) have been predicted to host significant RT topological photoresponses in low-frequency regions, especially in the THz gap, well addressing the shortcomings of THz detectors. However, such devices have not been experimentally realized yet. Herein, a type-II WSM (NbIrTe4 ) is selected to fabricate THz detector, which exhibits a photoresponsivity of 5.7 × 104  V W-1 and a one-year air stability at RT. Such excellent THz-detection performance can be attributed to the topological effect of type-II WSM in which the effective mass of photogenerated electrons can be reduced by the large tilting angle of Weyl nodes to further improve mobility and photoresponsivity. Impressively, this device shows a giant intrinsic anisotropic conductance (σmax /σmin  = 339) and THz response (Iph-max /Iph-min  = 40.9), both of which are record values known. The findings open a new avenue for the realization of uncooled and highly sensitive THz detectors by exploring type-II WSM-based devices.

Neural Dynamics Underlying Cognitive Control Modulated by Reinforcement Learning of Irrelevant Stimulus-Response Associations.

Human behavioral studies have shown that reward has multifaceted (motivational, learning, and emotional) effects on cognitive control. Past studies have extensively explored the neural underpinning of the motivational effect of reward on cognitive control, but less is known on the other components. The present study investigates the learning effect of reward on cognitive control with a novel paradigm reinforcing task-irrelevant stimulus-response (S-R) associations. We manipulated the contingency of irrelevant spatial stimulus-response-reward between participants (n = 54) in an orthogonal Simon task during EEG recording. The behavioral results showed that the orthogonal Simon effect in RTs and error rates increased or reversed when performance-contingent reward always followed spatially compatible or incompatible trials. The EEG results showed that the initial incorrect activation of the lateralized readiness potential, reflecting response preparation based on irrelevant spatial S-R associations, was present in the incompatible or compatible condition when reward always followed compatible or incompatible trials. Meanwhile, the P3b amplitude also showed a similar pattern of increase or reversal depending on the contingency of irrelevant stimulus-response-reward. These findings suggest that the brain used reward-strengthened irrelevant spatially compatible or incompatible S-R associations to predict responses. Moreover, the frontocentral N2 amplitude and theta band (4-8 Hz) power showed similar reward-related increase or reversal in the conflict effect, suggesting that there was conflict when the response predicted by the reward-strengthened irrelevant S-R associations was different from the correct response. Taken together, these results suggest that reinforcement learning of irrelevant spatial S-R associations can modulate cognitive control.

Great Enhancement Effect of 20-40 nm Ag NPs on Solar-Blind UV Response of the Mixed-Phase MgZnO Detector.

High-performance solar-blind UV detector with high response and fast speed is needed in multiple types of areas, which is hard to achieve in one device with a simple structure and device fabrication process. Here, the effects of Ag nanoparticles (NPs) with different sizes on UV response characteristics of the device are studied, the Ag NPs with different sizes that are made from a simple vacuum anneal method. Ag NPs with different sizes could modulate the peak response position of the mixed-phase MgZnO detector from near UV range (350 nm) to deep UV range (235 nm), and the enhancement effect of the Ag NPs on the UV response differs much with the crystal structure and the basic UV response of the MgZnO thin film. When high density 20-40 nm Ag NPs is induced, the deep UV (235 nm) response of the mixed-phase MgZnO detector is increased by 226 times, the I uv/I dark ratio of the modified device is increased by 17.5 times. The slight enhancement in UV light intensity from 20 to 40 nm Ag NPs induces multiple tunnel breakdown phenomena within the mixed-phase MgZnO thin film, which is the main reason for the abnormal great enhancement effect on deep UV response of the device, so the recovery speed of the modified device is not influenced. Therefore, Ag NPs with different sizes could effectively modulate the UV response peak position of mixed-phase MgZnO thin films, and the introduction of Ag NPs with high density and small size is a simple way to greatly increase the sensitivity of the mixed-phase MgZnO detector at deep UV light without decreasing the device speed.

Photo detection and modulation from 1,550 to 2,000†nm realized by a GeSn/Ge multiple-quantum-well photodiode on a 300-mm Si substrate.

A GeSn/Ge multiple-quantum-well (MQW) p-i-n photodiode structure was proposed for simultaneously realizing high detectivity photo detection with low dark current and effective optical modulation based on the quantum confined Stark (QCSE) effect. The MQW stacks were grown on a 300-mm Ge-buffered Si substrate using reduced pressure chemical vapor deposition (RPCVD). GeSn/Ge MQW p-i-n photodiodes with varying mesa diameters were fabricated and characterized. An ultralow dark current density of 16.3 mA/cm2 at -1 V was achieved as expected due to the low threading dislocation density (TDD) in pseudomorphic GeSn layer. Owing to the ultralow dark current density and high responsivity of 0.307 A/W, a high specific detectivity of 1.37×1010 cm·Hz1/2/W was accomplished at 1,550 nm, which is comparable with commercial Ge and extended-InGaAs photodetectors. Meanwhile, the bias voltage-dependent photo response was investigated from 1,700 to 2,200 nm. The extracted effective absorption coefficient of GeSn/Ge MQW shows a QCSE behavior with electric field-dependent exciton peaks from 0.688 to 0.690 eV. An absorption ratio of 1.81 under -2 V was achieved at 2 µm, which shows early promise for effective optical modulation. The high frequency response was calculated theoretically, and the predicted 3-dB bandwidth for the photodiode with a mesa diameter of 30 µm could reach 12 GHz at -2 V.

The immunogenicity of the virus-like particles derived from the VP2 protein of porcine parvovirus.

Porcine parvovirus (PPV) is a major cause of the syndrome of sow reproductive failure that can cause economic losses. In this study, we developed a subunit vaccine against porcine parvovirus (PPV), composed of virus-like particles (VLPs) derived from a prokaryotic system, and evaluated its potential against PPV infection. The soluble recombinant VP2 protein was expressed in E. coli Transetta(DE3) cells using a pCold II prokaryotic expression vector at a low temperature of 15 °C. After expression and purification, the recombinant VP2 protein was successfully assembled into VLPs with a similar shape of PPV viron and also hemagglutination activity. PPV VLPs formulated in a water-in-oil-in-water adjuvant evoked high hemagglutination inhibition antibody and neutralization antibody titres in both guinea pigs, used as reference model, and target species, pigs. Immunization with VLPs vaccine stimulated high hemagglutination inhibition antibody and neutralization antibody responses in guinea pigs, used as reference, and target species, weaned pigs, and primiparous gilts. PPV VLPs from E. coli yielded complete fetal protection against PPV infection in primiparous gilts immunized with a single-dose vaccine. PPV VLPs inhibited the replication and spread of PPV in primiparous gilts, which was confirmed by the detection of PPV DNA and infectious PPV in nasal and rectal swabs of challenged sows. These results suggest that VLPs-based PPV vaccine is a promising PPV vaccine candidate.

Reduction of Postweaning Multisystemic Wasting Syndrome-Associated Clinical Symptoms by Virus-Like Particle Vaccine Against Porcine Parvovirus and Porcine Circovirus Type 2.

The porcine circovirus type 2 (PCV2) capsid (Cap) protein and porcine parvovirus (PPV) VP2 protein have been studied in vaccines to control postweaning multisystemic wasting syndrome (PMWS). Virus-like particle (VLP) vaccines are nonreplicative vectors that deliver epitopes and induce immune responses. However, most VLP vaccines are recombinant proteins expressed in eukaryotic systems and are expensive and complex. In this study, the full-length PCV2-Cap and PPV-VP2 proteins were expressed in Escherichia coli, which self-assembled into VLPs. The highly soluble proteins were purified using Ni-chelating affinity chromatography. The proteins self-assembled into VLPs of ∼20 nm (Cap VLP) and 25 nm (VP2 VLP) in diameter. The immunogenicities of Cap VLP and VP2 VLP were determined in piglets coinfected with PPV and PCV2 postimmunization. The results suggested that Cap VLP and VP2 VLP did not antagonize each other. The combined vaccine induced stronger humoral and cellular immune responses and provided the best protection against PPV and PCV2 coinfection. On a farm containing PMWS-infected pigs, the combined Cap VLP and VP2 VLP vaccine significantly improved piglet growth indices; the average daily weight gains were significantly higher than those of the Cap VLP vaccine and nonimmunized groups. Thus, Cap and VP2 protein expression in E. coli is feasible for large-scale VLP vaccine production. The combined vaccine may be a promising candidate vaccine for better preventing PMWS-associated diseases coinfected with PCV2 and PPV.

Broadband Absorption Tailoring of SiO2/Cu/ITO Arrays Based on Hybrid Coupled Resonance Mode.

Sub-wavelength artificial photonic structures can be introduced to tailor and modulate the spectrum of materials, thus expanding the optical applications of these materials. On the basis of SiO2/Cu/ITO arrays, a hybrid coupled resonance (HCR) mechanism, including the epsilon-near-zero (ENZ) mode of ITO, local surface plasmon resonance (LSPR) mode and the microstructural gap resonance (GR) mode, was proposed and researched by systematically regulating the array period and layer thickness. The optical absorptions of the arrays were simulated under different conditions by the finite-difference time-domain (FDTD) method. ITO films were prepared and characterized to verify the existence of ENZ mode and Mie theory was used to describe the LSPR mode. The cross-sectional electric field distribution was analyzed while SiO2/Cu/ITO multilayers were also fabricated, of which absorption was measured and calculated by Macleod simulation to prove the existence of GR and LSPR mode. Finally, the broad-band tailoring of optical absorption peaks from 673 nm to 1873 nm with the intensities from 1.8 to 0.41 was realized, which expands the applications of ITO-based plasmonic metamaterials in the near infrared (NIR) region.

Identification of a RIP1 Kinase Inhibitor Clinical Candidate (GSK3145095) for the Treatment of Pancreatic Cancer.

RIP1 regulates cell death and inflammation and is believed to play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases and cancer. While small-molecule inhibitors of RIP1 kinase have been advanced to the clinic for inflammatory diseases and CNS indications, RIP1 inhibitors for oncology indications have yet to be described. Herein we report on the discovery and profile of GSK3145095 (compound 6). Compound 6 potently binds to RIP1 with exquisite kinase specificity and has excellent activity in blocking RIP1 kinase-dependent cellular responses. Highlighting its potential as a novel cancer therapy, the inhibitor was also able to promote a tumor suppressive T cell phenotype in pancreatic adenocarcinoma organ cultures. Compound 6 is currently in phase 1 clinical studies for pancreatic adenocarcinoma and other selected solid tumors.

Defect-Induced Tunable Permittivity of Epsilon-Near-Zero in Indium Tin Oxide Thin Films.

Defect-induced tunable permittivity of Epsilon-Near-Zero (ENZ) in indium tin oxide (ITO) thin films via annealing at different temperatures with mixed gases (98% Ar, 2% O2) was reported. Red-shift of λENZ (Epsilon-Near-Zero wavelength) from 1422 nm to 1995 nm in wavelength was observed. The modulation of permittivity is dominated by the transformation of plasma oscillation frequency and carrier concentration depending on Drude model, which was produced by the formation of structural defects and the reduction of oxygen vacancy defects during annealing. The evolution of defects can be inferred by means of X-ray diffraction (XRD), atomic force microscopy (AFM), and Raman spectroscopy. The optical bandgaps (Eg) were investigated to explain the existence of defect states. And the formation of structure defects and the electric field enhancement were further verified by finite-difference time domain (FDTD) simulation.

Tween-20 transiently changes the surface morphology of PK-15 cells and improves PCV2 infection.

BACKGROUND: Low concentrations of nonionic surfactants can change the physical properties of cell membranes, and thus and in turn increase drug permeability. Porcine circovirus 2 (PCV2) is an extremely slow-growing virus, and PCV2 infection of PK-15 cells yields very low viral titers. The present study investigates the effect of various nonionic surfactants, namely, Tween-20, Tween-28, Tween-40, Tween-80, Brij-30, Brij-35, NP-40, and Triton X-100 on PCV2 infection and yield in PK-15 cells. RESULT: Significantly increased PCV2 infection was observed in cells treated with Tween-20 compared to those treated with Tween-28, Tween-40, Brij-30, Brij-35, NP-40, and Triton X-100 (p < 0.01). Furthermore, 24 h incubation with 0.03% Tween-20 has shown to induce significant cellular morphologic changes (cell membrane underwent slight intumescence and bulged into a balloon, and the number of microvilli decreased), as well as to increase caspase-3 activity and to decrease cell viability in PCV2-infected PK-15 cells cmpared to control group; all these changes were restored to normal after Tween-20 has been washed out from the plate. CONCLUSION: Our data demonstrate that Tween-20 transiently changes the surface morphology of PK-15 cells and improves PCV2 infection. The findings of the present study may be utilized in the development of a PCV2 vaccine.

Laser induced photocatalytic activity enhancement of TiO2 thin films.

In this paper, the photocatalytic activity enhancement of TiO2 thin films was realized by laser irradiation. The H2 yield of the as-irradiated film is 79 µmol/(h*m2), which is 33% more than that of the as-deposited TiO2 film. Spectrophotometer, X-ray diffraction and Raman system were employed to characterize the samples. The results showed that both the scanning rate and line spacing of the laser modification have effects on photocatalytic activity. It suggests that a phase junction is formed between the amorphous and rutile phases. The increment of H2 generation could be attributed to the alignment of Fermi levels in the phase junction.

Interaction between graphene-coated nanowires revisited with transformation optics.

The interaction between graphene-coated nanostructures provides interesting optical properties not found in isolated graphene plasmonic structures. However, full-analytical solutions, which can provide deep physical insights underlying the hybrid graphene plasmonic systems, are difficult to achieve. In this Letter, we deploy the theory of transformation optics to study the plasmonic interactions between two dielectric-core-graphene-shell nanowires. The scattering and absorption spectra as well as the field distributions are derived analytically. We find that the interaction between two graphene-coated nanowires results in polarization-independent multi-frequency Fano dips, which show a broadband red shift of bonding modes and a blue shift of anti-bonding modes when the nanowires approach each other. The analytical tool presented here offers a rigorous study of graphene plasmonic compound and can be extended to treat more complicated cases.

Polarization invariant plasmonic nanostructures for sensing applications.

Optics-based sensing platform working under unpolarized light illumination is of practical importance in the sensing applications. For this reason, sensing platforms based on localized surface plasmons are preferred to their integrated optics counterparts for their simple mode excitation and inexpensive implementation. However, their optical response under unpolarized light excitation is typically weak due to their strong polarization dependence. Herein, the role of rotational symmetry for realizing robust sensing platform exhibiting strong optical contrast and high sensitivity is explored. Specifically, gammadion and star-shaped gold nanostructures with different internal and external rotational symmetries are fabricated and studied in detail, from which their mode characteristics are demonstrated as superposition of their constituent longitudinal plasmons that are in conductive coupling with each other. We demonstrate that introducing and increasing internal rotational symmetry would lead to the enhancement in optical contrast up to ~3x under unpolarized light illumination. Finally, we compare the sensing performances of rotationally symmetric gold nanostructures with a more rigorous figure-of-merit based on sensitivity, Q-factor, and spectral contrast.

Multifunctional Hyperbolic Nanogroove Metasurface for Submolecular Detection.

Metasurface serves as a promising plasmonic sensing platform for engineering the enhanced light-matter interactions. Here, a hyperbolic metasurface with the nanogroove structure in the subwavelength scale is designed. This metasurface is able to modify the wavefront and wavelength of surface plasmon wave with the variation of the nanogroove width or periodicity. At the specific optical frequency, surface plasmon polaritons are tightly confined and propagated with a diffraction-free feature due to the epsilon-near-zero effect. Most importantly, the groove hyperbolic metasurface can enhance the plasmonic sensing with an ultrahigh phase sensitivity of 30 373 deg RIU-1 and Goos-Hänchen shift sensitivity of 10.134 mm RIU-1 . The detection resolution for refractive index change of glycerol solution is achieved as 10-8 RIU based on the phase measurement. The detection limit of bovine serum albumin (BSA) molecule is measured as low as 0.1 × 10-18 m (1 × 10-19 mol L-1 ), which corresponds to a submolecular detection level (0.13 BSA mm-2 ). As for low-weight biotin molecule, the detection limit is estimated below 1 × 10-15 m (1 × 10-15 mol L-1 , 1300 biotin mm-2 ). This enhanced plasmonic sensing performance is two orders of magnitude higher than those with current state-of-art plasmonic metamaterials and metasurfaces.

Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases.

RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, we report our lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clinical candidate GSK2982772 (compound 5), currently in phase 2a clinical studies for psoriasis, rheumatoid arthritis, and ulcerative colitis. Compound 5 potently binds to RIP1 with exquisite kinase specificity and has excellent activity in blocking many TNF-dependent cellular responses. Highlighting its potential as a novel anti-inflammatory agent, the inhibitor was also able to reduce spontaneous production of cytokines from human ulcerative colitis explants. The highly favorable physicochemical and ADMET properties of 5, combined with high potency, led to a predicted low oral dose in humans.

DNA-Encoded Library Screening Identifies Benzo[b][1,4]oxazepin-4-ones as Highly Potent and Monoselective Receptor Interacting Protein 1 Kinase Inhibitors.

The recent discovery of the role of receptor interacting protein 1 (RIP1) kinase in tumor necrosis factor (TNF)-mediated inflammation has led to its emergence as a highly promising target for the treatment of multiple inflammatory diseases. We screened RIP1 against GSK's DNA-encoded small-molecule libraries and identified a novel highly potent benzoxazepinone inhibitor series. We demonstrate that this template possesses complete monokinase selectivity for RIP1 plus unique species selectivity for primate versus nonprimate RIP1. We elucidate the conformation of RIP1 bound to this benzoxazepinone inhibitor driving its high kinase selectivity and design specific mutations in murine RIP1 to restore potency to levels similar to primate RIP1. This series differentiates itself from known RIP1 inhibitors in combining high potency and kinase selectivity with good pharmacokinetic profiles in rodents. The favorable developability profile of this benzoxazepinone template, as exemplified by compound 14 (GSK'481), makes it an excellent starting point for further optimization into a RIP1 clinical candidate.

On-chip discrimination of orbital angular momentum of light with plasmonic nanoslits.

The orbital angular momentum (OAM) of light can be taken as an independent and orthogonal degree of freedom for multiplexing in an optical communication system, potentially improving the system capacity to hundreds of Tbits per second. The high compactness and miniaturization of devices required for optical communications impose strict requirements on discriminating OAM modes of light at a small (micro- or even nano-meter) scale for demultiplexing; these requirements represent a challenge for traditional OAM sorting strategies. Here, we propose a semi-ring plasmonic nanoslit to directly and spatially sort various OAM modes of light into ∼120 nm-spaced mode intervals on the metallic surface. Making use of the constructive interference of a helical-phase modulated surface wave excited by a vortex beam, this on-chip interval can be stably demonstrated both theoretically and experimentally with a quasi-linear dependence on the plasmonic wavelength. Furthermore, its immunity to semi-ring geometry (i.e., the radius and number of rings) is verified by simulations. As a result, OAM discriminating is guaranteed by this stable sorting function. This technique shows a viable solution to discriminate the OAM of light at the nano-scale and might lead to broad benefits across the fields of optical communications, plasmonic physics and singular optics.